Robotic management of superior mesenteric artery syndrome.

Wilkie's syndrome is an unusual cause of upper intestinal obstruction due to mechanical compression of the superior mesenteric artery (SMA) to the duodenum, with nonspecific symptoms, whose diagnosis is confirmed by angiotomography. Initially, the treatment is conservative to regain weight and restore mesenteric adipose tissue, associated with postural changes of the patient. If this fails, surgical treatment is indicated, being laparoscopic duodenojejunostomy described as the gold standard. Robotics' assistance is feasible and safe to carry out the procedure. We present the case of a 21-year-old male patient who comes with stabbing abdominal pain and persistent postprandial vomiting that has caused weight loss of 11 kilograms in the last 2 years without apparent cause, associated with gastroesophageal reflux. During the procedure, we evidenced open diaphragmatic pillars and duodenal compression due to SMA, and robotic-assisted laparoscopic hyatoplasty + Nissen fundoplication + duodenojejunostomy were performed without complications, with excellent post-surgical results.

Revisional surgery for persistent dysphagia plus Roux Y gastric bypass robot-assisted in a patient with obesity. About a case.

This case study presents a female patient with progressive dysphagia for solids, heartburn, and obesity that proved refractory to clinical management. Imagenological diagnosis revealed esophageal stenosis and achalasia. Furthermore, metabolic syndrome was established. We proposed intervention through esophagogastric reconstruction due to stenosis, revision of cardiomyotomy and robotic gastric bypass revealing scar tissue and fibrosis on the anterior aspect of the stomach resulting from prior fundoplication surgery. The patient underwent esophagogastric reconstruction due to adhesion bands which conditioned partial angulation of the gastroesophageal junction, cardiomyotomy revision, anterior and posterior hiatal plasty, and Roux Y Gastric Bypass assisted by a robot without complications. The intervention resulted in significant improvement in postoperative symptoms. This case highlights the importance of considering the probability of mechanical obstruction due to postsurgical adhesions in the initial evaluation of recurrent and persistent dysphagia, with surgical reintervention being the ideal option for resolution.

GLUT1, MCT1/4 and CD147 overexpression supports the metabolic reprogramming in papillary renal cell carcinoma.

Papillary Renal Cell carcinoma (pRCC) is the second most common type of RCC, accounting for about 15% of all RCCs. Surgical excision is the main treatment option. Still, 10 - 15 % of clinically localized tumours will recur and/or develop metastasis early after surgery, and no reliable prognostic biomarkers are available to identify them. It is known that pRCC cells rely on high rates of aerobic glycolysis, characterized by the up-regulation of many proteins and enzymes related with the glycolytic pathway. However, a metabolic signature enabling the identification of advanced pRCC tumours remains to be discovered. The aim of this study was to characterize the metabolic phenotype of pRCCs (subtypes 1-pRCC1 and 2-pRCC2) by evaluating the expression pattern of the glucose transporters (GLUTs) 1 and 4 and the monocarboxylate transporters (MCTs) 1 and 4, as well as their chaperon CD147. We analysed the clinico-pathological data and the protein and mRNA expression of GLUT1, GLUT4 and MCT1, MCT4 and CD147 in tumours from Porto and TCGA series (http://cancergenome.nih.gov/), respectively. With the exception of GLUT4, plasma membrane expression of all proteins was frequently observed in pRCCs. GLUT1 and MCT1 membrane overexpression was significantly higher in pRCC2 and significantly associated with higher pN-stage and higher Fuhrman grade. Overexpression of GLUT1, MCT1/4 and CD147, supports the metabolic reprograming in pRCCs. MCT1 expression was associated with pRCC aggressiveness, regardless of the tumour histotype.

Doble neuropatía como presentación de una crioglobulinemia tipo II no asociada a infección por virus de la hepatitis C / Cryoglobulinemia type II with double neuropathy not associated with hepatitis C infection

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Loss of mitochondrial SDHB expression: what is its role in diffuse thyroid lipomatosis?

Diffuse lipomatosis of the thyroid gland is a very rare disease, characterized by extensive infiltration of thyroid parenchyma by mature adipose tissue, usually not accompanied by amyloid fibrils deposition. The pathophysiology of adipose tissue infiltration in the thyroid gland remains unknown. We report a clinical case of a diffuse thyroid lipomatosis, whose immunohistochemical study of succinate dehydrogenase - subunit B (SDHB) revealed loss of expression of this protein in the follicular or adipose cells. We detected the presence of a recently described SDHB gene large deletion. Loss of mitochondrial SDHB expression may have a key role in understanding the pathophysiology of thyrolipomatosis, by regulating status of lipid metabolism.

How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer.

Well-differentiated thyroid carcinomas comprise two well-defined histological types: papillary and follicular (PTCs and FTCs, respectively). Despite being derived from the same cell (thyroid follicular cell), these two types of tumour accumulate distinct genetic abnormalities during progression. The molecular pathology of thyroid cancer is now better understood because of our ability to identify RET/PTC rearrangements and BRAF mutations in the aetiopathogenesis of the large majority of PTCs and the high prevalence of RAS mutations and PAX8/PPARgamma rearrangements in follicular patterned carcinomas (FTCs and follicular variant of PTCs). This review summarises most of the molecular alterations currently used as targets for new biological treatments and looks at some of the changes that are already occurring or may occur in the treatment of patients with thyroid cancer. For simplicity, the review is divided up according to the major genetic alterations identified in well-differentiated thyroid carcinomas (RET/PTC rearrangements, BRAF mutations, RAS mutations and mitochondrial DNA deletions and mutations) and their respective treatments.

Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid.

Oxyphil or Hurthle cell tumours of the thyroid are characterised by their consistent excessive number of mitochondria. A recently discovered gene, GRIM-19 has been found to fulfil two roles within the cell: as a member of the interferon-beta and retinoic acid-induced pathway of cell death, and as part of the mitochondrial Complex I assembly. In addition, a gene predisposing to thyroid tumours with cell oxyphilia (TCO) has been mapped to chromosome 19p13.2 in one family. A cluster of genes involved in mitochondrial metabolism occurs in this region; one of these is GRIM-19. We have searched for GRIM-19 mutations in a series of 52 thyroid tumours. Somatic missense mutations in GRIM-19 were detected in three of 20 sporadic Hurthle cell carcinomas. A germline mutation was detected in a Hurthle cell papillary carcinoma arising in a thyroid with multiple Hurthle cell nodules. No mutations were detected in any of the 20 non-Hurthle cell carcinomas tested, nor in any of 96 blood donor samples. In one of the sporadic Hurthle cell papillary carcinomas positive for GRIM-19 mutation, we have also detected a ret/PTC-1 rearrangement. No GRIM-19 mutations were detected in any of the six cases of known familial Hurthle cell tumour tested, so that our results do not support the identification of GRIM-19 as the TCO gene. The GRIM-19 mutations we have detected are the first nuclear gene mutations specific to Hurthle cell tumours to be reported to date; we propose that such mutations can be involved in the genesis of sporadic or familial Hurthle cell tumours through the dual function of GRIM-19 in mitochondrial metabolism and cell death.

Microsatellite instability, mitochondrial DNA large deletions, and mitochondrial DNA mutations in gastric carcinoma.

Mitochondrial DNA (mtDNA) large deletions and mtDNA mutations have been demonstrated in various types of human cancer. The relationship between the occurrence of such alterations and the nuclear microsatellite instability (MSI) status of the neoplastic cells remains controversial. In an attempt to clarify the situation in gastric carcinoma, we studied, by PCR/SSCP and sequencing, five mitochondrial genes and two D-loop regions in 32 gastric carcinomas that had been previously screened for MSI and mitochondrial common deletion. MtDNA alterations were detected in 26 carcinomas (81%). All the mtDNA mutations, which occurred mainly in the D-loop and ND1 and ND5 genes, were transitions. D-loop alterations (insertions and/or deletions) were not significantly associated with mutations in the coding regions. There was a trend towards an inverse relationship between the occurrence of mitochondrial common deletion and mtDNA mutations. No significant relationship was observed between MSI status and mtDNA mutations, whereas the mitochondrial common deletion appeared to be almost exclusively restricted to MSI-negative tumors. The latter finding--almost no gastric carcinoma with MSI-positive phenotype has large deletions of mtDNA--needs to be confirmed in a larger series and in tumors from other organs.

Abnormalities of the E-cadherin/catenin adhesion complex in classical papillary thyroid carcinoma and in its diffuse sclerosing variant.

The cadherin/catenin complex regulates cellular adhesion and motility and is believed to function as an invasion suppressor system. Several studies have identified alterations in the expression profiles of those molecules in different histotypes of thyroid carcinoma. The diffuse sclerosing variant (DSV) of papillary thyroid carcinoma (PTC) is a rare, highly invasive variant of PTC in which an impairment of cell-cell adhesion may play a major role. In an attempt to progress in the understanding of the clinicopathological features of DSV, this study examined eight cases of DSV, 18 cases of classical PTC and a control group of normal thyroid by immunohistochemistry (E-, P- and N-cadherins and beta-, gamma- and alpha-catenins). The E-cadherin gene was also studied by polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) and methylation-specific PCR (MSP). In contrast to classical PTC, which showed heterogeneous loss of E-cadherin expression, in almost every case of DSV a pronounced reduction was observed in its membranous expression, accompanied by a relocation to the cytoplasm. Inactivation of the E-cadherin/catenin complex appears to occur in DSV via two different pathways: E-cadherin alteration either through mutation (one out of the eight cases) or through methylation of the E-cadherin gene promoter (three out of five cases); and beta- and/or gamma-catenin alterations (three of the eight cases). Methylation of the E-cadherin gene promoter, abnormalities of E-cadherin expression and alterations of gamma-catenin were also detected in classical PTC. In DSV, as in classical PTC, there is neo-expression of P-cadherin in areas of squamous metaplasia and no N-cadherin expression. In conclusion, abnormalities of the E-cadherin/catenin complex appear to be more pronounced in DSV than in classical PTC. It remains to be shown whether or not such differences are associated with the more aggressive behaviour of DSV compared with classical PTC.

A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency.

Mutations in the PKLR gene responsible for pyruvate kinase (PK)-deficient anaemia are mainly located in the coding regions: 11 are in the splicing sites and, recently, three mutations have been described in the promoter region. We now report a novel point mutation A-->G on nucleotide 72, upstream from the initiation codon of the PKLR gene, in four Portuguese PK-deficient patients. This new regulatory mutation occurs within the most proximal of the four GATA motifs (GATA-A element) in the R-type promoter region. In two patients who were homozygous for this mutation, a semiquantitative reverse transcription polymerase chain reaction (PCR) procedure was used to evaluate the amount of R-PK mRNA transcript in the reticulocytes. The mRNA level was about five times lower than in normal controls, demonstrating that the PKLR gene transcription is severely affected, most probably because the -72A-->G point mutation disables the binding of the erythroid transcription factor GATA-1 to the GATA-A element. Supporting these data, the two patients homozygous for the -72A-->G mutation had severe haemolytic anaemia and were transfusion dependent until splenectomy. Two other patients who were compound heterozygous for this mutation and the previously described missense mutation 1456C-->T had a mild condition.

Hürthle cell tumours of the thyroid. A review with emphasis on mitochondrial abnormalities with clinical relevance.

The molecular and enzymatic abnormalities of mitochondria in oxyphilic / oncocytic / Hürthle cells and their respective tumours are reviewed in a series of sections: "Mitochondria, ageing, neurodegenerative diseases and cancer", "Mitochondrial abnormalities in Hürthle cells and Hürthle cells tumours", "Mitochondrion-related alterations in tumours with and without Hürthle cell/oncocytic features", "True and secondary oxyphilia", and "Bcl-2 expression, apoptosis and necrosis in Hürthle cell tumours and tumour-like lesions". The clinicopathological and pathogenetic meaning of the data on record on these topics are discussed, with an emphasis on thyroid pathology.